1,721,032 research outputs found
Contrast agents for magnetic resonance angiographic applications: 1H and 17O NMR relaxometric investigations of two gadulinium(III) DTPA-like chelates endowed with high binding affinity to human serum albumin
No full textThe relaxometric properties of two Gd(III)DTPA-like complexes (DTPA = diethylenetriamine-N,N,N,N--pentaacetic acid) bearing different substituents for binding to human serum albumin (HSA) are compared. In spite of the structural differences of the recognition synthon and of the residual electric charge, the two chelates display an analogous binding affinity for the serum protein. Upon formation of the adducts with HSA, the exchange rates of the coordinated water appear slowed down by an amount corresponding to ca. 50% of the rates found for the free complexes. The relaxivity of [Gd(BOM)3DTPA (H2O)]2 - is significantly higher than that of MS-325 either in the free complex or in the macromolecular adduct. Finally, the effect of pH on the stability of the HSA adducts and on the values of their relaxivities has been investigated
Green Synthesis of a Hyaluronan-Based Multimeric A9 Peptide System: Polysaccharide-A9 Conjugate with Enhanced HER2 Receptor Binding Affinity and Potential Biomedical Applications as an Active Material
Full text link: A solid-state strategy for conjugating the peptide sequence A9 to hyaluronic acid (HA) has been developed via mechanosynthesis promoted by microwave radiation. The method employs a silica-supported nucleophilic catalyst (DMAP) to activate the carboxylic groups of the polysaccharide, enabling efficient conjugation. These conditions minimize waste generation, enhancing environmental sustainability and operator safety while ensuring a high yield of the final HA-A9 conjugate. The multicopy HA-A9 system exhibits enhanced affinity toward a synthetic HER2 receptor model. Furthermore, the HA-A9 conjugate demonstrates the ability to self-assemble into micellar aggregates and form viscous materials enriched with β-sheet peptide structures. These supramolecular assemblies highlight the potential of conjugates for biomedical applications
Thio-conjugation of substituted benzofurazans to peptides: molecular sieves catalyze nucleophilic attack on unsaturated fused rings
Full text linkBioconjugates of 2,1,3-benzoxadiazole (benzofurazan) and its derivatives have attracted considerable
interest due to their biological activities and applications as fluorescent tags. A high-yield, chemoselective,
and mild procedure for the S-alkylation of cysteine containing peptides by benzofurazan halogenides is
reported. The key feature of this procedure is the use of activated molecular sieves (MS) to catalyze thiol
activation for nucleophilic substitution under very mild conditions (room temperature and no need for
added bases). To the best of our knowledge, this is the first report about thiol nucleophilic substitution
performed on unsaturated and annelated systems catalyzed by activated molecular sieves. Reaction yields
were remarkable even with benzofurazans having weakly activating groups or no activating groups at all.
The potential of the new methodology was explored by synthesizing fluorescent, hydrophilic
benzofurazan/peptide conjugates, also with peptides containing unprotected lysine residues
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Long Acidic Tail of High Mobility Group Box 1 (HMGB1) Protein Forms an Extended and Flexible Structure That Interacts with Specific Residues within and between the HMG Boxes
No full textHMGB1 (high mobility group B1) is a conserved chromosomal protein composed of two similar DNA binding domains (HMG box A and box B) linked by a short basic stretch to an acidic
C-terminal tail of 30 residues. The acidic tail modulates the DNA binding properties of HMGB1, and its length differentiates the various HMGB family members. We synthesized a peptide that corresponds to the acidic tail in HMGB1 (T-peptide) and studied its binding to the single boxes and to the fragment corresponding to tailless HMGB1 (designated as ABbt fragment). CD spectroscopy showed that T-peptide stabilizes significantly the ABbt fragment and that the complex has an identical thermal stability as fulllength HMGB1. Calorimetric and NMR data showed that T-peptide binds with a dissociation constant of 9 íM to box A and much more weakly to box B. 1H-15N HSQC spectra of full-length HMGB1 and of the ABbt fragment are very similar; the small chemical shift differences that exist correspond to those residues of the ABbt fragment that were affected by the addition of the T-peptide. We conclude that the T-peptide mimics closely the acidic tail and that the basic stretch and the acidic tail form an extended and flexible segment. The tail interacts with specific residues in the boxes and shields them from other interactions
Silicon phthalocyanines functionalized with axial substituents targeting PSMA: synthesis and preliminary assessment of their potential for PhotoDynamic Therapy of prostate cancer
Full text linkPhotodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitor are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)2 and SiPc-OSi(PSMAi)2. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si−O−C) bond for SiPc-PQ(PSMAi)2, and a silyloxy (Si−O−Si) bond for SiPc-OSi(PSMAi)2. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)2 showed a higher singlet oxygen quantum yield ΦΔ, higher fluorescence quantum yields ΦF and better photostability than SiPc-OSi(PSMAi)2. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(−) PC3-FLU cells. However, SiPc-PQ(PSMAi)2 showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions
Exofacial protein thiols as a route for the internalization of Gd(III)-based complexes for MRI cell labelling
No full textFour novel MRIGd(III)-based probes have been synthesized and evaluated for their labeling properties on cultured cell lines K562, C6, and B16. The labeling strategy relies upon the fact that cells display a large number of reactive exofacial protein thiols (EPTs) that can be exploited as anchorage points for suitably activated MRI probes. The probes are composed of a Gd(III) chelate (based on eitherDO3A or DTPA) connected through a flexible linker to the 2-pyridyldithio chemical function for binding to EPTs. GdDO3A-based chelates could efficiently label cells (up to a level of 1.2 1010 Gd(III) atoms/cell), whereas GdDTPA-based chelates showed poor or no cell labeling ability at all. Among the GdDO3A based compounds, that having the longest spacer (compound GdL1A) showed the best labeling efficacy. The mechanism of EPT mediated cell labeling by GdL1A involves probe internalization without sequestration of the Gd(III) chelate within subcellular structures such as endosomes
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